Immune perturbations have become recognized and expected as common life threatening consequences of thermal injury. Clinical control of these patient immune problems is one of the major goals of burn therapy. We are, however, greatly limited by our lack of knowledge concerning the basic mechanisms underlying these clinical effects. We have proposed the following studies as a means to add to our understanding of those basic mechanisms. In the three years we have worked on this project, we have shown that burn victims often experience a profound immune depression which is both clinically significant and long-lasting. Such immune depression appears to be limited to compromise of T cell function which is expressed clinically in the prolongation of survival of unmatched allograft skin, and increased Gram negative and fungal sepsis. experimentally, we have solid evidence that a serum-borne suppressor participates in the development of suppressor T cells. Therefore, we propose to continue this work with efforts to delineate endogenous immunosuppression both functionally and chemically. Specific aims include 1) identification of immunosuppressive serum samples from non-septic burn patients that are contamination and endotoxin free, 2) definition of the immunosuppressive agent by immunochemical methodology, emphasizing the demonstration of E series prostaglandins and interferon, 3) testing immunosuppressive isolates in vivo using a mouse model, and 4) isolation of immunosuppressive lymphokines from burn patient lymphocyte culture supernatants and testing the relationship of their suppressive activity to that of serum-borne suppressor.